From the group of earthy alkalies we can exclude the first and last member: beryllium, a rare element in the earth which has no physiologic and so far as we know no pharmacologic significance. Radium indeed belongs chemically to this group, but its actions are so dominated by the decomposing radiations that it seems more suitable to consider it later in connection with the other radio- active element, uranium.
There remain the important physiologic elements, magnesium and calcium, which appear with many similarities and many opposites in the organism and then strontium and barium, closely related to calcium but foreign to the body. Common to all is their appearance as divalent cations. They are not so movable and exchangeable as the alkali cations. The relation of the earthy alkalies to water is likewise different and their salts are poorly soluble. Likewise they are in opposition to the univalent cations in their influences upon colloids. Yet magnesium stands in an intermediate position, and it also has a special position chemically opposite to the heavier elements of the group.
In the actions on the organism the group relationships of these four elements comes distinctly into appearance.
Magnesium has a circulation in the earth similar to that of calcium between the lithosphere and hydrosphere: it is found in the upper earth surface in great amounts (about 2.5 per cent; calcium about 3.5 per cent) chiefly as the carbonate, alone as magnesite and together with calcium carbonate, as dolomite. As the chloride and sulphate it is associated with potassium salts. Even in this natural appearance it comes now with potassium and now with calcium salts, so that the intermediate position of magnesium between the alkalies and earthy alkalies holds even in relation to the organism.
Magnesium is obviously present in every living cell, indeed in the muscle and nervous tissue the strongest; in the cerebrospinal fluid the magnesium content is higher than in the serum. These are the first suggestions of the very dark role in general of magnesium in the animal organism.
Magnesium metabolism proceeds very slowly. In the serum with its content of 2-4 mg. per cent it is present essentially in smaller amounts than calcium. Just as with calcium it exists there only in part as a free cation, and in other parts bound as a complex anion. One might conceive of this as the first reserve. In any case organic compounds are present in the cells. In the bones the affinity for magnesium is much less than that for calcium.
The physiologic significance of magnesium is best known in the green plants. Here Willstaetter has discovered it in an organic form in chlorophyl- similar to the iron in hemoglobin. One presumes that in the assimilation of carbon dioxide, also a synthetic reduction process, it plays a role similar to that of iron in hemoglobin in the oxidation of carbon compounds. Also in organic chemistry magnesium is often used in synthetic reactions as an intermediator for the introduction of a new radicle. Grignard has shown a catalytic promotion of organic synthesis with organic magnesium compounds. in physiologic animal investigation no great weight is placed upon the presence of magnesium, because Ringer’s solution does not contain magnesium, while on the other hand Tyrode’s solution contains half as much MgCl2 as CaCl2. Probably the greater significance comes to magnesium in the interior of the cell.
ION ACTION ON COLLOIDS AND CELLS
In the influence on colloids magnesium takes a mid position between the alkalies and the earthy alkalies. In its swelling capacity, for example, it stands nearer the alkalies, also in protein salting out and flocculation. The precipitation of hydrophile colloids, perhaps albumin, is reversible through magnesium salts, as with the alkali salts and in concentrations, in which calcium, strontium and barium salts cause irreversible precipitates. For many colloidal effects, as the precipitation of suspension colloids, the positive double valence of magnesium is decisive and in this respect magnesium agrees with the other earthy alkalies as calcium, strontium and barium, and like the other earthy alkalies as an antagonist to sodium and potassium. But outside of the antagonism between the uni- and divalent cations as it appears in living colloids there is also an opposition in the action of magnesium and calcium in the living cell wall as the latter is antagonist of not only magnesium but also the alkalies, which in many cases cause precipitation through swelling. On muscle a swelling action of magnesium has been demonstrated in contradistinction to the de-swelling through calcium. For placing magnesium in equilibrium relatively more calcium is necessary than for sodium and potassium. In an antagonism which manifests itself in the removal of a one-sided damaging influence, the concentration relations are always important.
That the actions of two elements which follow one another in a related group are not additive but subtractive and appear in the end-effects as opposites is something very common as we have already seen in sodium and potassium, and which also occurs with chloride and bromine. This is probably connected with an opposing property of penetration so that closely related ions collect on the site of action, the surface of the colloidal particles. Increased introduction of magnesium provokes an increased excretion of calcium into the urine; thereby calcium goes out of its tissue compounds into ionic form. By increase of the magnesium content in the serum, the binding. capacity of the cartilage for calcium is impaired.
An antagonism between magnesium and calcium can be demonstrated on the frog heart. Addition of magnesium to the nutrient fluid slows the heart beat, lengthens diastole and ends finally in standstill in diastole (this action is also shown from intravenous injections on the entire animal) while reversely calcium increase accelerates the cardiac action, lengthens systole and finally leads to systolic standstill. The cardiac standstill from magnesium can be removed through calcium (in a half molar concentration) so that the heart again begins to beat. The excitation of ventricular autonomy through he injection of calcium and barium is possible but does not succeed with magnesium. In such experiments magnesium in general has a tonus-lessening, vagus-stimulating influence but not in the degree of potassium. In physiologic concentration a co-effect of magnesium for equilibrium in the heart is not evident, since magnesium as already stated can be omitted from the nutrient fluid without any change. On the isolated preparation of bronchial musculature a lessening of tonus is also demonstrated.
The intestinal action of magnesium salts need not be concerned with a purgative action as is known of magnesium sulphate. With MgSO4 the fluidity of the stool depends not upon a resorptive action but exactly on the poor resorption of this salt. This saline purgative substance, MgSO4 dissociates very little and has a slight capacity for diffusion: therefore the difficult absorption. The withdrawal of fluid into the intestine is according to all appearances conditioned through an increase of pure intestinal fluid. Through the difficult absorption of this salt, the fluid is held in the intestine and compels the intestine to excrete it.
Intestinal peristalsis by MgSO4 as well as by MgCl2 is depressed as well as by intravenous introduction. In the stomach of animals MgSO4 slows emptying, but increases the gastric secretion. But in man the secretion has also been found depressed.6 According to Wiechmann the magnesium paralysis of the intestine can be removed through calcium; Botazzi on the contrary discusses a synergism of magnesium and calcium.
In any case it may be assumed that magnesium and calcium have some similarity in the intestinal action even if the experimental findings are still contradictory to one another.
By MgSO4 a relaxation of the sphincter Oddi (choledochus) is produced, so that there is increased emptying of the gallbladder. The secretion of bile from the liver is rather depressed.9
The magnesium ions have an important relation to the nervous system. Injected in large doses (decigrams), the magnesium salts provoke a narcotic condition. At first a peripheral paralysis appears, and indeed like a curare effect in that the muscles loses indirect excitability. The respiratory muscles are uninvolved for some time. To this is added then a central paralysis with loss of consciousness. An increase in magnesium in the brain has not been observed quantitatively in single intoxications and only to a slight extent in repeated poisonings. After intralumbar injections motility and sensation in the lower half of the body diminish. The magnesium narcosis can be immediately interrupted through the intravenous injection of calcium, from which it may be presumed that it is concerned with an ion action. But in this antagonism of ions positively nothing is said of calcium acting stimulating on the nervous system by itself. The opposite is much more the case.
The magnesium narcosis is an effect of large doses and does not ordinarily occur after oral administration because of the poor absorption of magnesium salts. By the addition of saponins the absorption is increased so that narcosis can be orally obtained. The special affinity of the nervous system expresses itself in the anesthesia appearing after subcutaneous injection. It is worthy of note that a transient hypersthesia accompanies the pain of injection and the itching of the skin, and also an irritation of the sensory nerves through the magnesium ions.
The body temperature is reduced by magnesium injections as well as by calcium injections.
Of great interest in respect to the homoeopathic use of magnesium salts in dysmenorrhea are the studies of Watchorn. These show a dependence of the pain at the menstrual period upon the variations of magnesium content of the blood. With pains the magnesium in the serum increases. By doses of magnesium before the menses severe pains could be produced in women who otherwise had no pain at the menstrual period. On the contrary, in the premenstrual nausea they found low magnesium values and were able to relieve this nausea by doses of magnesium acetate.
The favorable action of the administration of magnesium in para-thyreo-privic tetany is probably to be traced to the liberation of tissue-bound calcium into an ionic form.
Use has been made of the narcotic cell action by a preponderance of magnesium over calcium ions in tetanus, eclampsia and uremia, which naturally could be only palliative. There is still no explanation for the narcotic action. Perhaps the following finding in the suspension colloids points the way: an oil-water phase is shifted through magnesium in the direction of water in oil, through calcium to oil in water. In the significance of cell lipoids for the narcotic action, perhaps by this pattern a bridge might be built from experimental to clinical observations.
Very extensive conclusions for the physiologic significance and the therapeutic evaluation of magnesium salts have been drawn by P. Delbet from studies and analysis. Animals which have been fed with a scurvy-producing diet remain alive about twice as long when magnesium salts are injected or added to the diet. From this he concludes that a favorable effect on the metabolism through magnesium according to the nature of vitamin. Delbet perceives magnesium as particularly important in respect to germination; in the plant magnesium is very abundant in the seed and more is found in the corm than in the straw. Mice become sterile in the absence of magnesium. Sperm are especially rich in magnesium and the introduction of magnesium is supposed to stimulate sexual function. In children the thymus is rich in magnesium, in the adult, the brain and testes, and with old age the calcium in the testes increases; on the contrary, magnesium diminishes. A number of old-age phenomena were favorably influenced according to his report when magnesium was regularly introduced: old people become more able to work, sexual function is stimulated, muscle stiffness is lessened or remove, likewise senile tremor and pruritus senilis. Studies on the healthy with the use of magnesium chloride solution gave an increase in well being and general activity. With overstrained mental, activity, it should, just as has been shown of the phosphate, become free to a great extent and appear in the urine. Muscles, brain and sexual glands were said to be, corresponding to their high content of magnesium, the chief points of functional and therapeutic attack of magnesium. Indeed, even Parkinsonian syndromes and ataxia were said to improve under the introduction of magnesium salts.
But Delbet goes still farther. Proceeding from favorable magnesium effects in skin diseases, warts, papilloma, polyps, he presents a study on mice with artificial tumors and reports a favorable influence. Defect of magnesium in the diet favors the development of carcinoma. Use of magnesium should be preventive in carcinoma and indeed even exert a favorable influence after its development according to him.
Corresponding to his theory of magnesium deficiency the therapy is a continuous introduction of magnesium as a nutrient material. This is necessary in only small amounts as in the case of other materials, cognizance being taken of the facts of magnesium metabolism. A confirmation of the very extensive assertions of Delbet must be awaited.
The local mass action of magnesium sulphate as a laxative is, just as little as the use of magnesia usta for the neutralization of gastric acid, to be ascribed to specific magnesium action.
MAGNESIUM CARBONICUM Type
The type of magnesium carb. is relaxed and sensitive to cold as with all alkalies and earthy alkali carbonates. One can say that in many respects magnesium acts toward calcium as sodium to potassium, but even more distinct is the intermediate position between potassium and calcium. Exactly as in natrium carb. is the relaxation paired with great sensitivity, bodily (against contact, cold air, cold water) as also psychic which makes the patient seem irritable, ill humoured and anxious. The magnesium type is represented preferably by women and children. In general chilliness and tendency to emaciation (the last in contrast to calcareas!) and offensive greasy night sweats are shown by magnesium patients. The relaxation involves also a great part of the musculature as with kali carb., and we recall here the magnesium function in the muscle cells. Indeed, a sunken sinking to the ground without loss of consciousness has been reported by Hahnemann. This is comparable to the sudden weakness in the extremities. To a much greater extent than sodium, potassium and calcium carbonates is magnesium carbonicum rich with pains, full of neuralgias, darting, tearing, boring (with magnesium phosphoricum preferably spasmodic). The pains are worse during rest, the patient must stand and move about. Cold and contact aggravate, warmth and firm pressure relieve the pains.
If Delbet has been as favorable primary actions of large doses of magnesium salts, an increase of the bodily and mental energy, then this does not contradict the states of exhaustion which appear in the provings under other conditions. In the effect there is not only the amount but also the time factor, the frequency of the dose and the duration of observations; moreover, the previous state of the individual and many other factors.
Sleep with magnesium carbonicum is unrefreshing; the patient is more tired morning than evening. From 2 to 3 he is sleepless, must arise and move about. Magnesium muriaticum has sleeplessness with great anxiety and restlessness in bed. Both remedies have desire for sleep during the day.
A very outstanding trend is represented by the effects of magnesium salts on the peripheral nerves. It seems logical to bring this into relationship with the experimentally demonstrated narcotic action and anesthesia. An irritative phase is less observed in the experiments, outside of sensitivity to pain and the crawling which precedes the anesthesia for a time. But drug proving on the healthy has particularly brought out this important action phase for therapy. Magnesium cab. has severe pains in the nerve trunks; the patient cannot sit still but must move about. With all magnesium salts these pains are worse at night. In provings of magnesium carb. these neuralgias appear chiefly in the head and face, particularly nocturnally, at rest an unbearable toothache, or nocturnal, tearing; at night must get up and walk about. The toothache is said to occur at every change in the weather; it is worse before the menses and during pregnancy. Also a back and sacral pain, nocturnal, as if bruised, belongs to the picture of pain of magnesium carb., as do general soreness, stiffness and aching. A quick, penetrating gluteal pain, pain in the shoulders and arms so that they fall heavily when elevated, in the legs as after toil-walking is difficult- all these symptoms show that outside of the sensory nerves, the muscles are involved.
The organ actions of magnesium carb. go, as with all magnesium salts, predominantly on the gastro-intestinal canal and on the sexual organs, particularly the uterus. For these organ effects, the lower potencies are preferable. Indeed, it is demonstrated that magnesium is predominantly excreted through the intestine and thereby gastro-intestinal effects can occur. This part of the magnesium picture has much in common with the gastro-intestinal symptoms of calcium carb. Entirely as with calcium, in magnesium carb. is a striking presence of acid in the gastro-intestinal canal: sour taste, sour eructations, sour vomiting, sour belching. The tongue and oral mucosa burn, are sensitive, especially towards acid. In the diarrhea of children it is especially noteworthy: the entire child smells sour, the stools are sour. The diarrhea is preceded by knife-like pains in the abdomen. A remarkable symptom appears with magnesium carb. exactly as with calcium: Milk passes through undigested or the stool is watery and contains clumps looking like tallow. Possibly this is to be referred to the saponification of fats through the earthy alkalies. An especially striking symptom for magnesium carb. in diarrhea is: green appearance of the stool, like a scum in a frog pond. It is also not to be forgotten that magnesium just like calcium has a significant effect on the motility and secretion of the gastro-intestinal canal, which can be explained only insufficiently at present from the ionic effects on the motor apparatus. The fact that milk is poorly borne my be associated with the abnormal acid status. (Neither aversion nor desire for flesh is characteristic, for both are seen in the provings; similarly contradictory are the desire and aversion for green vegetables).
The dyspeptic disturbances in nurslings may become severe even to athrepsia, just as in calcarea carb. Prevailing in magnesium carb. are diarrhea, but also hard, crumbly dry stools, which are difficult to evacuate, are reported and it is characteristic for their vegetative basis that they appear after psychic excitation or mental exertion. Constipation is otherwise more characteristic of magnesium muriaticum. Colicky, knife_like constrictive gastric or abdominal pains often precede the dyspeptic disturbances.
Just as calcium so does magnesium have a close connection with the menstrual event. The findings cited from Watchorn also suggest this. While with the other magnesium salts both too early and too profuse menses are reported, it is more often the case with magnesium carb. that the menses are late or entirely suppressed. For all the magnesium salts it holds that the menstrual blood is very dark and tar-like. Cited as characteristic for the carbonate is that the blood flows markedly at night and ceases when walking around. Here a vegetative influence on the tone of the uterus is to be considered in explanation. Many complaints exist before and during the menses; so for magnesium carb. there are chills, colds particularly in the throat, chilliness, backache and toothache before each menstrual period as well as facial pallor during the period; slimy discharge with lower abdominal cramps is of subordinate significance.
Of the atonic symptoms in the male sexual apparatus are decreased libido and frequent pollutions, in the urinary organs inability to retain and the involuntary passage of urine are reported in the provings.
Less utilized are the skin symptoms of magnesium carb., which are very similar to those of calc. carb. Only the dryness and itching of magnesium are more prominent. Magnesium, however, cannot reach the same rank as calcarea as a remedy for scrofula.
Stauffer reports that magnesium carb. has proven itself in cataract. The cloudy vision of the inflamed eye, Like a feather before it, from Hahnemann’s provings, does not given sufficient basis for it and other explanations are not available.
The chloride compound of magnesium, MgCl2, has the same type and the same modalities as magnesium carb. but also deviations which make the remedy in many directions similar to natr. mur. This holds particularly for the type of constipation. Moreover, a marked action upon the biliary secretion has been ascribed to magnesium mur.
A good indication for magnesium mur. is the headache which is relieved by firm pressure and warm covering. This corresponds to the usual magnesium modalities, but is emphasized in the headache of this compound.
With magnesium mur. constipation with hard stools which are so dry that they crumble when they emerge from the anus, prevails. The stool is like sheep dung and is evacuated only with much pressure. While this syndrome is mentioned merely incidentally in magnesium carb. with magnesium muriaticum it has proven an indication and recalls the dry constipation of natrium mur.
The connection of magnesium mur. to the liver is depicted in the following manner: the liver is hard and enlarged, there is a pressing pain in the liver region which is worse on lying on the right side; when lying on the left side there is a feeling of a weight tearing across. With this a gray-white stool and jaundice should be present. These are very distinct manifestations of biliary stasis in which the constipation described might be considered as a supporting factor. We recall that magnesium salts rapidly empty the gallbladder by a mass effect, but depress bile formation. This experimental finding appears as a reversed effect which forms the opposite to the homoeopathic employment. In the completely different experimental conditions this is not amazing.